This study will investigate the efficacy of levodopa in improving the neurodevelopment and movement disorders in children with Angelman Syndrome (AS), a rare neurodevelopmental disorder with a prevalence of approximately 1 in 10,000 to 1 in 20,000 individuals. AS is characterized by mental retardation, limited speech, seizures, abnormal movements such as tremors, and ataxic gait. Currently, there is no cure for AS and treatment is largely supportive. Calcium/calmodulin-dependent kinase type 2 (CaMKII) is an enzyme in post-synaptic neurons that is involved in the formation of memory and learning. Recently, it was shown that excess phosphorylation of CaMKII may be responsible for some of the neurological deficits seen in AS. Levodopa (LD) is a prodrug that delivers dopamine to the brain. It is usually given with carbidopa (CD), a peripheral decarboxylase inhibitor, to increase the bioavailability of LD. Animal studies have suggested that LD can reverse the excess phosphorylation of some enzymes involved in synaptic and neuronal function, including CaMKII. More recent data have shown that exogenous LD given to both wild-type and AS mice reduces the phosphorylation of CaMKII in the brain and leads to improvements in the motor learning and performance of the AS mice. Therefore, it is hypothesized that oral LD/CD will lead to an improvement in the neurodevelopment and movement disorder in children with AS. Oral LD/CD has been used in at least 12 AS children between 15 months and 21 years old. However, no controlled studies have been carried out to date to evaluate use of LD/CD in children or adults. The specific aim of this study is to conduct a Phase 2 randomized double-blind placebo-controlled trial of LD/CD in AS children between 4 years and 12 years old. Children with AS will be recruited for this study through parent support groups and professional organizations. One hundred AS children will be randomized equally to receive either placebo or LD/CD and observed on therapy for one year. Outcome measures that will be used in this study include the Bayley Scales of Infant and Toddler Development, the Vineland Adaptive Behavior Scales, the Preschool Language Scale, the Aberrant Behavior Checklist, as well as a modified version of the Unified Parkinson Disease Rating Scale. Upon completion of the first year of the Phase 2 trial, all subjects will be offered the option of continuing on LD/CD for an additional year in an open-label study to obtain longer-term safety, and possibly efficacy data in a larger cohort of subjects.